Conventional vaccines against infectious viruses or microorganisms frequently employ inactivated or live-attenuated pathogen. Disadvantages of such vaccine preparations include difficulty in large-scale production, safety considerations in handling, and the risks involved in immunizing elderly or immunodeficient individuals with live-attenuated vaccines.
Subunit vaccines, which utilize isolated components of a virus particle, are a safer alternative to conventional vaccines. The components are typically recombinant proteins or synthetic short peptides. However, most subunit vaccines, like most soluble antigens, generally elicit only a humoral immune response, which stimulates B-lymphocytes to produce antibodies. Such a response is effective in attacking bacteria and viruses in the extracellular media, but not in the elimination of intracellular bacteria, parasites and virus-infected cells. For maximum effectiveness, a vaccine should also be able to elicit a CTL (cytotoxic T-lymphocyte) response. The CTL response stimulates the production of “killer” T-lymphocytes, which attack cells perceived as abnormal, including virus-infected cells.
The mode of processing and presentation of an antigen determines which T cell subtype (helper or cytotoxic) is activated during the immune response. In the exogenous (Class II) pathway, exogenous antigens enter an antigen presenting cell (APC) via endocytosis or a related mechanism. The proteins then undergo proteolysis, yielding peptides having 10–20 amino acids, which bind to MHC-II molecules. The resulting complexes stimulate CD4+ (helper) T cells, which regulate humoral immune responses. In the endogenous (Class I) pathway, proteins present in the cytoplasm, such as viral proteins, are degraded to peptides 8–10 amino acids in length, which bind to MHC-I molecules. The resulting complexes interact with CD8+ (cytotoxic) T-lymphocytes (CTL). As noted above, this response is especially important for protection against virus-infected cells or intracellular microorganisms.
Accordingly, it is desirable to provide immunogenic compositions which produce an effective CTL immune response, particularly for use with soluble antigens.